Adrenocorticotrophin-Induced Hypertension in Kats

Abstract

Adrenocorticotrophin (ACTH) administration raises blood pressure in humans, sheep, and the rat. ACTH hypertension can be reproduced in sheep by combined infusion of aldosterone, 17 alpha-OH-progesterone, and 17 alpha,20 alpha-OH-progesterone, and in humans by cortisol. In the rat, ACTH hypertension is probably due to corticosterone. Progesterone treatment can prevent ACTH-induced hypertension in sheep. This study examined the ability of progesterone to antagonize the onset and development of ACTH-induced hypertension in Sprague-Dawley rats (n = 44). We also investigated the relationship of plasma digoxin-like substances (DLS) to ACTH hypertension. ACTH (0.5 mg/kg/day) significantly increased blood pressure (+24 +/- 5 mm Hg, P < .001) in association with an increase of water intake, urine output, and plasma sodium concentration, and a decrease of body weight and plasma potassium concentration. ACTH increased plasma DLS (+132 +/- 18 pg/mL, P < .01), and there was a positive correlation between DLS and blood pressure (r = 0.68, n = 22, P < .001). Progesterone (50 mg/kg/day) did not block the development of ACTH-induced hypertension in the rat. Although progesterone prevented the ACTH-induced rise in plasma sodium and glucose concentration, it did not prevent the decrease in plasma potassium concentration. The failure of progesterone to prevent ACTH-induced hypertension in the rat argues against a common "hypertensinogenic" mechanism for ACTH hypertension in sheep and rat. DLS may play a role in ACTH-induced hypertension in the rat.